cagrilintide/semaglutide (CagriSema) / Novo Nordisk - LARVOL DELTA

RAMBO: The Role of the Amylin Analogue Cagrilintide in Bone Metabolism (clinicaltrials.gov) - P1 | N=144 | Recruiting | Sponsor: Novo Nordisk A/S | Not yet recruiting ➔ Recruiting

Enrollment open • Genetic Disorders • Obesity

CagriSema drives weight loss in rats by reducing energy intake and preserving energy expenditure. (PubMed, Nat Metab) - "CagriSema is a combination of amylin (cagrilintide) and glucagon-like peptide-1 (semaglutide) analogues being developed for weight management...By contrast, pair-feeding causes less-pronounced weight loss, while weight matching requires a 51% decrease in food intake. Therefore, approximately one-third of CagriSema's weight loss efficacy arises from an effect on energy expenditure, the blunting of metabolic adaptation, which contributes to the successful treatment of obesity."

Journal • Preclinical • Genetic Disorders • Obesity

Incretin-based therapies for the treatment of obesity-related diseases. (PubMed) - "Liraglutide, semaglutide and tirzepatide are incretin-based therapies currently approved by FDA for the management of obesity, while triple GIPR/GCGR/GLP-1R agonist retatrutide (LY3437943), the cagrilintide/semaglutide (CagriSema) 2.4 mg combination, high-dose oral semaglutide, and oral orforglipron are in advanced stages of development...Moreover, incretin-based therapies have also been proven beneficial on obesity-related comorbidities, such as knee osteoarthritis (KOA), obstructive sleep apnea (OSA) syndrome, and MASLD. Further research is needed to improve our understanding of their effects on obesity-related comorbidities and the underlying mechanism, whether involving direct effects on target tissues or mediated by improvement in BW, glucose levels and other CV risk factors."

Journal • Review • Cardiovascular • Congestive Heart Failure • Diabetes • Genetic Disorders • Heart Failure • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity • Obstructive Sleep Apnea • Osteoarthritis • Pain • Respiratory Diseases • Rheumatology • Sleep Disorder • Type 2 Diabetes Mellitus

Synergy in Action: Novel Combination Strategies for DKD: New Horizons in DKD: Emerging Diagnostic and Therapeutic Approaches (KSN 2025) - "The lecture will then explore the revolutionary potential of multi-receptor agonists—including dual GLP-1/GIP agonists (tirzepatide), triple GLP-1/GIP/glucagon agonists (retatrutide, mazdutide), and novel combinations like amycretin and cagrisema—which may fundamentally "remodel" the metabolic phenotype of DKD...Special consideration will be given to Asian populations, where lower BMI but high metabolic risk may offer unique opportunities for these novel combinations. The lecture will conclude with a vision for precision medicine in DKD."

Chronic Kidney Disease • Diabetic Nephropathy • Genetic Disorders • Metabolic Disorders • Nephrology • Obesity • Renal Disease

REDEFINE1: a randomised study of combined semaglutide 2.4 mg and cagrilintide 2.4 mg for the treatment of overweight or obesity in adults (EASD 2025) - P3 | "CagriSema provided robust and clinically meaningful weight reduction in adults with overweight and obesity, superior to sema or cagri alone, with a well-tolerated safety profile consistent with other incretin-based therapies."

Clinical • Metabolic Disorders • Obesity

REDEFINE 2: a randomised trial of combined semaglutide 2.4 mg and cagrilintide 2.4 mg for the treatment of adults with BMI ≥27kg/m2 and type 2 diabetes (EASD 2025) - P3 | "Clinical Trial Registration Number: NCT05394519 Background and aims: Semaglutide and cagrilintide monotherapies have been shown to induce weight loss... CagriSema provided clinically meaningful weight reduction and improvements in metabolic health in adults with BMI ≥27 kg/m2 and T2D, with tolerability comparable to other incretin-based therapies."

Clinical • Diabetes • Hypoglycemia • Metabolic Disorders • Type 2 Diabetes Mellitus

A Study of How CagriSema Works on Appetite in People With Excess Body Weight (clinicaltrials.gov) - P1 | N=164 | Active, not recruiting | Sponsor: Novo Nordisk A/S | Trial primary completion date: Dec 2025 ➔ Apr 2025

Trial primary completion date • Genetic Disorders • Obesity

Mechanisms for the preservation of energy expenditure during CagriSema-induced weight loss in obese rats (EASD 2025) - "Here, we studied molecular mechanisms involved in the prevention of metabolic adaptation during CagriSema-induced weight loss.Materials and Diet-induced obese rats were treated with vehicle or CagriSema (cagrilintide: 2 nmol/kg and semaglutide: 2 nmol/kg) for 20 days... Taken together, we conclude that CagriSema treatment prevents metabolic adaptation partly by preventing a reduction in mitochondrial proton leak in skeletal muscle. In addition, the multi-omics signature indicates that CagriSema-induced weight loss, in contrast to weight loss by diet restriction, bypasses the normal molecular adaptations to weight loss in metabolically active tissues. Human trials are required to determine the translatability and clinical relevance of these findings."

Preclinical • Diabetes • Metabolic Disorders • Obesity

Update on the clinical trials using CagriSema (EASD 2025) - No abstract available

Clinical • Metabolic Disorders • Obesity

MET-233 Is an Ultra-Long-Acting Amylin Receptor Agonist (ADA 2025) - "The pharmacokinetics of MET-233 and cagrilintide were compared after single administration in pigs... The long half-life of MET-233 observed in pigs suggests that infrequent administration in humans may be achievable. Results from chronic administration to rats indicate that MET-233 is highly effective, and additive impact on body weight was observed when coadministered with MET-097. The potency, durability, and combinability of MET-233 and MET-097 highlight the potential of MET-233 as a differentiated treatment option."

Metabolic Disorders • Obesity

Effect of Combined Therapy with Once-Weekly Subcutaneous Cagrilintide 2.4 mg and Semaglutide 2.4 mg (CagriSema) on Energy Intake, Gastric Emptying, and Appetite in Adults with Overweight or Obesity (ADA 2025) - P1 | "CagriSema contributes to weight management in adults with overweight or obesity by significantly reducing energy intake and appetite without delaying GE."

Clinical • Late-breaking abstract • Diabetes • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Cagrisema-Induced Weight Loss in Diet-Induced Obese Rats Relies on Preserved Mitochondrial Leak Respiration in Skeletal Muscle (ADA 2025) - "In rats, CagriSema (CS), a combination of semaglutide (a GLP-1 analogue) and cagrilintide (an amylin analogue), prevents metabolic adaptation, but the mechanisms behind this effect are unknown.Objective: To investigate the effects of CS on metabolic efficiency in two of the most energy consuming organs - liver and skeletal muscle. Diet-induced obese male rats were subjected to vehicle or CS treatment (2+2 nmol/kg of semaglutide and cagrilintide) for 20 days (n=13). CS prevents metabolic adaptation to weight loss partly by preventing a reduction in mitochondrial leak respiration in skeletal muscle. Omics profiles and other functional mechanisms are currently under investigation."

Preclinical • Metabolic Disorders • Obesity

Symposium - Efficacy and Safety of CagriSema 2.4mg/2.4mg in Adults with Overweight/Obesity—The REDEFINE 1 and REDEFINE 2 Clinical Trials (ADA 2025) - No abstract available

Clinical • Metabolic Disorders • Obesity

Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity. (PubMed, N Engl J Med) - P3 | "Cagrilintide-semaglutide provided significant and clinically relevant body-weight reductions in adults with overweight or obesity, as compared with placebo. (Funded by Novo Nordisk; REDEFINE 1 ClinicalTrials.gov number, NCT05567796.)."

Journal • Cardiovascular • Constipation • Diabetes • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Metabolic Disorders • Obesity • Pain

Cagrilintide-Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes. (PubMed, N Engl J Med) - P3 | "Once-weekly cagrilintide-semaglutide (at a dose of 2.4 mg each) resulted in a significantly lower body weight than placebo in adults with obesity and type 2 diabetes. (Funded by Novo Nordisk; REDEFINE 2 ClinicalTrials.gov number, NCT05394519.)."

Journal • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Novo Nordisk A/S: CagriSema 2.4 mg / 2.4 mg demonstrated 22.7% mean weight reduction in adults with overweight or obesity in REDEFINE 1, published in New England Journal of Medicine (GlobeNewswire) - P3 | N=3,400 | REDEFINE 1 (NCT05567796) | P3 | N=1,200 | REDEFINE 2 (NCT05394519) | Sponsor: Novo Nordisk A/S | "These data, along with the related phase 3 REDEFINE 2 study...were presented...at the...ADA 85th Scientific Sessions and published in NEJM....The REDEFINE 1 trial found that treatment with CagriSema resulted in greater weight loss of 22.7% at 68 weeks versus 2.3% in the placebo group if all patients adhered to treatment. When evaluating the treatment effect regardless of adherence, those treated with CagriSema achieved statistically significant weight loss of 20.4% at 68 weeks versus 3.0% for the placebo group....In REDEFINE 2, if all participants adhered to treatment, the estimated mean change in body weight from baseline to week 68 was -15.7% with CagriSema versus -3.1% with placebo. When applying the treatment policy estimand, the estimated mean change in body weight from baseline to week 68 was-13.7% with CagriSema versus –3.4% with placebo."

P3 data • Obesity

A Research Study to Look at How Well CagriSema Helps People Living With Obesity Lose Weight and Maintain Weight Loss in the Long-term (clinicaltrials.gov) - P3 | N=600 | Recruiting | Sponsor: Novo Nordisk A/S | Not yet recruiting ➔ Recruiting

Enrollment open • Genetic Disorders • Obesity

A Research Study to Look at How Well CagriSema Helps People Living With Obesity Lose Weight and Maintain Weight Loss in the Long-term (clinicaltrials.gov) - P3 | N=600 | Not yet recruiting | Sponsor: Novo Nordisk A/S

New P3 trial • Genetic Disorders • Obesity

Novo Nordisk starts new CagriSema weightloss drug trial (TradingView) - "Novo Nordisk NOVO_B has launched a new late-stage trial for its experimental next-generation obesity drug candidate, CagriSema, as it tries to reassure the market of its potential after disappointing data from two previous studies."

Trial status • Obesity

Novo Nordisk to present array of new portfolio data including studies with semaglutide and CagriSema, expanding evidence in obesity and diabetes care at ADA 2025 (PRNewswire) - "Novo Nordisk today announced that new data from its industry-leading cardiometabolic portfolio will be showcased at the upcoming American Diabetes Association (ADA) 85th Scientific Sessions taking place in Chicago, June 20 – 23, 2025. A total of 29 abstracts will be presented, including trials investigating the efficacy and safety of CagriSema in people with overweight/obesity (REDEFINE 1) and those with overweight/obesity and type 2 diabetes (REDEFINE 2). Further, new data will complement the extensive body of cardiometabolic and kidney evidence for semaglutide in people with type 2 diabetes through analyses of the SOUL, STRIDE and FLOW trials, as well as insights from additional real-world studies in adults with obesity."

Clinical data • Obesity • Peripheral Arterial Disease • Type 2 Diabetes Mellitus

RAMBO: The Role of the Amylin Analogue Cagrilintide in Bone Metabolism (clinicaltrials.gov) - P1 | N=144 | Not yet recruiting | Sponsor: Novo Nordisk A/S

New P1 trial • Genetic Disorders • Obesity

Effects of NNC0194-0499, Cagrilintide, and Semaglutide Alone or in Combinations on Liver Damage and Alcohol Use in People With Alcohol-related Liver Disease (clinicaltrials.gov) - P2 | N=270 | Active, not recruiting | Sponsor: Novo Nordisk A/S | Recruiting ➔ Active, not recruiting

Enrollment closed • Hepatology

CagriSema: Data from P3 REDEFINE 4 trial (NCT06131437) for obesity in 2026 (Novo Nordisk) - Q1 2025 Results

P3 data • Obesity

Amylin: From Mode of Action to Future Clinical Potential in Diabetes and Obesity. (PubMed, Diabetes Ther) - "In individuals with advanced β-cell dysfunction, supplementing insulin therapy with pramlintide, the first and currently only approved injectable short-acting selective analog of amylin, has demonstrated efficacy in enhancing both postprandial and overall glycemic control in both type 2 diabetes (T2D) and type 1 diabetes (T1D) without increasing the risk of hypoglycemia or weight gain...As such, amylin agonists (combined with other members of the incretin class) could represent the elusive drug candidate to address the multi-hormonal dysregulations of diabetes subtypes and qualify as a precision medicine approach that surpasses the long overdue division into T1DM and T2DM. Further development of amylin-based therapies or delivery systems is crucial to fully unlock the therapeutic potential of this intriguing hormone.Graphical abstract available for this article."

Journal • Review • Cardiovascular • Diabetes • Genetic Disorders • Hypoglycemia • Metabolic Disorders • Obesity • Type 1 Diabetes Mellitus • Type 2 Diabetes Mellitus

Financial report for the period 1 January 2025 to 31 March 2025 (GlobeNewswire) - "Novo Nordisk still expects to file for the first regulatory approval of CagriSema during the first quarter of 2026."

Approval • Obesity